Esthetics with prosthetics in case of maxillary canine transposition: A clinical report

Transposition is a dental anomaly manifested by a positional interchange of two permanent teeth. The maxillary permanent canine usually transposes with the first premolar and occasionally with the lateral incisor. These are mainly genetically governed and are treated orthodontically if complete segment of tooth is present; in case of missing teeth, participation of cosmetic dentist is must. The present case report describes a situation where left canine to lateral incisor complete transposition was present along with a missing left central incisor. Esthetic rehabilitation of the “smile zone” was the major concern. Scrupulous treatment planning to esthetically contour transposed teeth according to their normal positions, i.e., transposed left canine to lateral incisor and transposed left lateral incisor to canine with replacement of missing tooth, was a challenge. Keywords: Canine transposition, composite veneers, smile designNigerian Journal of Clinical Practice •Jan-Mar 2012 • Vol 15 • Issue

Cholecalciferol supplementation and angiogenic markers in chronic kidney disease

Vitamin D plays an important role in proliferation and differentiation of cells and deficiency of vitamin D disturbs angiogenic balance. Previous studies in animal models have reported an association between serum levels of vitamin D and balance between pro- and anti-angiogenic factors. There is insufficient evidence about the effect of vitamin D on mediators of angiogenesis in patients with CKD. We investigated the effect of cholecalciferol supplementation on serum levels of angiogenic markers in non-diabetic patients with CKD stage 3-4. In this secondary analysis on stored samples of our previously published randomized, double-blind, placebo-controlled trial, stable patients of either sex, aged 18-70 years, with non-diabetic CKD stage 3-4 and vitamin D deficiency (serum 25-hydroxyvitamin D ≤20 ng/ml) were randomized to receive either two directly observed oral doses of cholecalciferol (300,000 IU) or matching placebo at baseline and 8 weeks. The primary outcome was change in brachial artery flow-mediated dilatation at 16 weeks. Changes in levels of serum angiogenesis markers (angiopoietin-1, angiopoietin-2, VEGF-A, VEGEF-R, and Tie-2) between groups over 16 weeks were compared. A total 120 patients were enrolled. Supplementation with cholecalciferol led to significant improvement in FMD. Serum 25(OH)D levels were similar in both groups at baseline (13.21±4.78 ng/ml and 13.40±4.42 ng/ml; p = 0.888). At 16 weeks, the serum 25(OH)D levels increased in the cholecalciferol group but not in the placebo group (between-group difference in mean change:23.40 ng/ml; 95% CI, 19.76 to 27.06; p<0.001). Serum levels of angiogenic markers were similar at baseline. At 16 weeks, angiopoietin-2 level decreased in cholecalciferol group (mean difference:-0.73 ng/ml, 95%CI, -1.25 to -0.20, p = 0.002) but not in placebo group (mean difference -0.46 ng/ml, 95%CI, -1.09 to 0.17, p = 0.154), however there was no between-group difference at 16 weeks (between-group difference in mean change: -0.27 ng/ml, 95%CI, -1.09 to 0.55, p = 0.624). Serum angiopoietin-1 level increased [mean change: 5.63 (0.51 to 10.75), p = 0.018] and VEGF-R level decreased [mean change: -87.16 (-131.89 to -42.44), p<0.001] in placebo group but did not show any change in cholecalciferol group. Our data shows the changes in Ang-1, Ang-2 and Ang-1/Ang-2 ratio after high dose oral cholecalciferol supplementation in patients with non-diabetic G3-4 CKD. The data suggests changes in circulating levels of angiogenic markers which needs to be confirmed through an adequately powered study

Deferred pre-emptive switch from calcineurin inhibitor to sirolimus leads to improvement in GFR and expansion of T regulatory cell population: a randomized, controlled trial

BACKGROUND: Measures to prevent chronic calcineurin inhibitor (CNI) toxicity have included limiting exposure by switching to sirolimus (SIR). SIR may favorably influence T regulator cell (T(reg)) population. This randomized controlled trial compares the effect of switching from CNI to SIR on glomerular filtration rate (GFR) and T(reg) frequency. METHODS: In this prospective open label randomized trial, primary living donor kidney transplant recipients on CNI-based immunosuppression were randomized to continue CNI or switched to sirolimus 2 months after surgery; 29 were randomized to receive CNI and 31 to SIR. All patients received mycophenolate mofetil and steroids. The main outcome parameter was estimated GFR (eGFR) at 180 days. T(reg) population was estimated by flowcytometry. RESULTS: Baseline characteristics in the two groups were similar. Forty-eight patients completed the trial. At six months, patients in the SIR group had significantly higher eGFR as compared to those in the CNI group (88.94 ± 11.78 vs 80.59 ± 16.51 mL/min, p = 0.038). Patients on SIR had a 12 mL/min gain of eGFR of at the end of six months. Patients in the SIR group showed significant increase in T(reg) population at 30 days, which persisted till day 180. There was no difference in the adverse events in terms of number of acute rejection episodes, death, infections, proteinuria, lipid profile, blood pressure control and hematological parameters between the two groups. Four patients taking SIR developed enthesitis. No patient left the study or switched treatment because of adverse event. CONCLUSIONS: A deferred pre-emptive switch over from CNI to SIR safely improves renal function and T(reg) population at 6 months in living donor kidney transplant recipients. Registered in Clinical Trials Registry of India (CTRI/2011/091/000034)

Effect of Interlayer Composition on the Properties of Laser-Directed-Energy-Deposition-Based Additively Manufactured Copper-Stainless Steel Wall Structures

Laser-directed energy deposition (LDED) is one of the advanced techniques used for the sustainable manufacturing of engineering components with minimal material wastage and higher performance. This paper reports an investigation on LDED-based additive manufacturing of compositionally graded Copper (Cu)-stainless steel (SS) wall structures for improved performance of tooling components. Three different approaches, such as Cu-SS direct joint, 20% graded Cu-SS, and 50% graded Cu-SS, are used to build the wall structures. Optical microscopy of LDED-built graded samples reveals defect-free deposition of Cu-SS direct joint and 50% graded Cu-SS wall structures at identified process parameters, whereas the 20%-graded wall yields micro-cracks in the lower Cu region. The elemental distribution shows gradual traditions in the weight percentages of Cu and Fe along the built wall. Furthermore, the ultimate tensile strengths of the direct Cu-SS joint wall structure and the 50%-graded Cu-SS wall structure are higher than the strength of LDED-deposited Cu, while the 20%-graded Cu-SS wall structure has lower ultimate tensile strength than the strength of LDED-deposited Cu. Lower ultimate strength and failure in the lower-Cu zone of 20% graded Cu-SS wall structure can be attributed to the presence of micro-cracks in the Cu 20SS 80 zone of 20%-graded Cu-SS wall structures. The study establishes LDED as a technique for building multi-material components promoting sustainability in terms of manufacturing and component performance.</p

Vitamin D deficiency, endothelial function and bone biomarkers in post-kidney transplantation patients from North India.

PURPOSE: CKD patients after kidney transplantation continue to suffer from elevated CV events which may be related to low vitamin D and its adverse impact on vascular function. The prevalence of vitamin D deficiency in North Indian kidney transplantation patients and its impact on vascular and bone biomarkers is unknown which this study investigated. METHODS: Non-diabetic, stable, > 6 months post-kidney transplantation patients, not on vitamin D supplementation, were recruited after informed consent. Data on demographics, anthropometrics and treatment were collected. Blood samples were stored at - 80 °C until analysis for bone and endothelial cell biomarkers using standard ELISA techniques. RESULTS: The clinical characteristics were: age 37.4 ± 9.9 years, 80% men, 27% ex-smokers, BP 125.5 ± 15.7/78.6 ± 9.7 mmHg, cholesterol 172.0 ± 47.8 mg/dL, hemoglobin 12.6 ± 2.3 g/dL, calcium 9.5 ± 0.6 mg/d and iPTH 58.4 ± 32.9 ng/mL and vitamin D 36.5 ± 39.8 nmol/L. Patients with vitamin D < 37.5 nmol/L (66%) had similar age, serum creatinine, serum phosphate, iPTH, blood pressure but lower calcium (9.3 ± 0.7 vs. 9.6 ± 0.5 mg/dL; p = 0.024), lower FGF23 (median 18.8 vs. 80.0 pg/mL; p = 0.013) and higher E-selectin (15.8 ± 7.9 vs. 13.0 ± 5.5 ng/mL; p = 0.047). On Univariate analysis, E-selectin (r = - 0.292; p = 0.005), FGF23 (r = 0.217; p = 0.036) and calcium (r = 0.238; p = 0.022) were significantly correlated with vitamin D levels. On stepwise multiple regression analysis, only E-selectin was associated with vitamin D levels (β = - 0.324; p = 0.002). CONCLUSION: Vitamin D deficiency was common in kidney transplant recipients in North India, associated with low FGF23 and high E-selectin. These findings suggest further investigations to assess the role of vitamin D deficiency-associated endothelial dysfunction, its implications and reversibility in kidney transplantation recipients

Effect of vitamin D supplementation on serum sclerostin levels in chronic kidney disease.

Vitamin D deficiency, cardiovascular disease and abnormal bone mineral metabolism are common in chronic kidney disease (CKD). Abnormal bone mineral metabolism has been linked to vascular calcification in CKD. Sclerostin has emerged as an important messenger in cross talk between bone-vascular axis. We analyzed sclerostin in subjects who participated in the randomized, double blind, placebo controlled trial investigating the effect of cholecalciferol supplementation on vascular function in non-diabetic CKD stage G3-4 and vitamin D ≤20ng/ml [CTRI/2013/05/003648]. Patients were randomized (1:1) to receive either two directly observed oral doses of 300,000 IU of cholecalciferol or matching placebo at baseline and 8 weeks. Of the 120 subjects enrolled, 58 in the cholecalciferol group and 59 in the placebo group completed the study. At baseline, serum levels of sclerostin were similar in both groups (cholecalciferol - median;190pg/ml, IQR;140-260pg/ml and placebo - median;180pg/ml, IQR; 140-240pg/ml, p=0.67). 16 weeks after cholecalciferol supplementation, there was no change in level of sclerostin (mean change;1.10 pg/ml, 95%CI; -27.34 to 29.34 pg/ml, p=0.25). However, a significant decrease in sclerostin level was noted in the placebo group (mean change; -31.94pg/ml, 95%CI; -54.76 to -9.13 pg/ml, p=0.002). Change (Δ) in sclerostin level at 16 weeks correlated negatively with Δ eGFR (r=-0.20, p=0.03) and positively with Δuric acid (r=0.37, p<0.001) but not with Δ25(OH) D (r=0.06, p=0.54), Δ iPTH (r=-0.03, p=0.78) ΔFGF23 (r=-0.08, p=0.38) and Δ1,25 (OH)2 D (r=-0.04, p=0.65). In conclusion, high dose cholecalciferol supplementation did not change sclerostin levels in non-diabetic stage 3-4 CKD subjects

Cytochrome c Reduction by H2S Potentiates Sulfide Signaling.

This is the author accepted manuscript. The final version is available from American Chemical Society via the DOI in this record.Hydrogen sulfide (H2S) is an endogenously produced gas that is toxic at high concentrations. It is eliminated by a dedicated mitochondrial sulfide oxidation pathway, which connects to the electron transfer chain at the level of complex III. Direct reduction of cytochrome c (Cyt C) by H2S has been reported previously but not characterized. In this study, we demonstrate that reduction of ferric Cyt C by H2S exhibits hysteretic behavior, which suggests the involvement of reactive sulfur species in the reduction process and is consistent with a reaction stoichiometry of 1.5 mol of Cyt C reduced/mol of H2S oxidized. H2S increases O2 consumption by human cells (HT29 and HepG2) treated with the complex III inhibitor antimycin A, which is consistent with the entry of sulfide-derived electrons at the level of complex IV. Cyt C-dependent H2S oxidation stimulated protein persulfidation in vitro, while silencing of Cyt C expression decreased mitochondrial protein persulfidation in a cell culture. Cyt C released during apoptosis was correlated with persulfidation of procaspase 9 and with loss of its activity. These results reveal a potential role for the electron transfer chain in general, and Cyt C in particular, for potentiating sulfide-based signaling.This work was supported by the French State in the frame of the “Investments for the future” Programme IdEx Bordeaux, reference ANR-10-IDEX-03-02, and by an ATIP-AVENIR grant (to M.R.F.), the National Institutes of Health (GM112455 to R.B. and R01GM113030 to M.D.P.), the Medical Research Council, UK (MR/M022706/1 to M.W.), the National Science Foundation (DGE-1309047 to A.K.S.), and the Brian Ridge Scholarship (R.T.). The authors are grateful to M.-F. Giraud for the help with purification of mitochondria

Anion-induced ferroelectric polarization in a luminescent metal–organic cage compound

A cage assembly consisting of an axially symmetric nonpolar octahedral [Zn6L8] core exhibits an interesting multifunctional luminescence and ferroelectric order at room temperature. The ferroelectric response originates from the toggling of nitrate anions and solvate molecules found in pockets between the cages.</p